Abstract
Background Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1α, IL-6, and TGF-β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF-β. A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β-catenin levels in tumor tissues. Results miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF-β, and β-catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.
Highlights
Hepatoblastoma is considered to be originated from undifferentiated liver cells in embryonic development [1, 2]
Extracellular vesicles (EVs) Were Successfully Isolated from Tumor Tissues
We aimed to isolate the EVs from hepatoblastoma and adjacent normal tissues, and transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to identify the EVs
Summary
Hepatoblastoma is considered to be originated from undifferentiated liver cells in embryonic development [1, 2]. We explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct, SRY, and TGF-β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. MiR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44 + CD90+ CD133+ cells and increased the expression of IL-6, Oct, SRY, TGF-β, and β-catenin in tumor tissues of mice. Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.